A chiral packed capillary column (PCC) was prepared by a photonic crystal fiber (PCF) as the frit and cellulose tris(3,5-dimethylphenylcarbamate)-coated silica particles (CDMPC@SiO2) as the chiral stationary phase. This column coupled with UV detection was employed for the enantioseparation of chiral compounds derived from traditional Chinese medicines (TCMs). Baseline enantioseparation was achieved for schisandrin B and tetrahydropalmatine, whereas partial separation was observed for anisodamine and corynoxeine. The reproducibility and stability of the column were confirmed, with relative standard deviation (RSD) values for retention time and resolution ranging from 2.5% to 3.2% (intra-day), 2.7% to 3.5% (inter-day), and 4.1% to 4.5% (inter-column). Then, the column was successfully applied to the direct enantioseparation and quantitative determination of tetrahydropalmatine in the extract of Yanhusuo (Corydalis Rhizoma). These results demonstrate that the proposed chiral CDMPC@SiO2 PCC is not only reproducible and stable but also can be effectively applied to the enantioseparation and content determination of chiral compounds in complex TCMs. Furthermore, density functional theory (DFT) calculations were conducted to investigate intermolecular interactions between CDMPC and chiral analytes, which provides a deeper understanding of the enantioseparation mechanism.
Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). 2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019). Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis. European Respiratory Society, Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Janssen, Lifearc, Roche, Verona Pharma, Zambon, National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, Program of the Shanghai Shenkang Development Center, EU/European Federation of Pharmaceutical Industries and Associations, Innovative Medicines Initiative, and Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium.
Medical cosmetology is a rapidly developing subspecialty of aesthetic medicine that deals with cosmetic issues like pigmentation, skin aging, and adipose deposition. Located between cosmetic surgery and everyday skin and beauty care, the method typically has a high safety profile, few adverse effects, and a quick recovery time. Nevertheless, there are still concerns about the biocompatibility of some of the cosmetic ingredients, as well as the problem of possible safety and the prevalence of allergic reactions. To overcome these limitations, traditional Chinese medicine (TCM) herbs, which are natural plant-based, are considered as safe and biocompatible. The focus of this review is to understand the molecular and biological pathways and therapeutic targets of the most common issues in medical cosmetology. We then review existing literature on TCM herbs and their active constituents that target these conditions. Additionally, recent achievements in the study and practical application of TCM herbs using modern transdermal drug delivery systems (TDDS) are presented. This paper, as a review, offers an innovative approach to the combination of TCM herbs and modern biomedical engineering strategies to be used in medical cosmetology.
Atherosclerosis (AS) is widely recognized as the principal pathological substrate underlying chronic cardiovascular diseases (CVDs). It is a chronic, progressive, and inflammatory disease characterized by excessive lipid deposition, oxidative stress, inflammatory response, plaque formation and rupture, thrombosis and vascular calcification (VC). Vascular smooth muscle cells (VSMCs) are essential for maintaining the normal structure of blood vessels and play a pivotal role in the pathological process of AS. Their proliferation, migration, differentiation, senescence and death processes critically influence the progression of AS. The specific mechanism of VSMCs participating in AS remains a central focus of research in the cardiovascular field. In recent years, natural products have garnered considerable attention in the field of AS prevention and treatment, primarily due to their multi-target effects, low toxicity and side effects. However, there is still a lack of systematic review of natural compounds that alleviate AS by regulating the function of VSMCs. This article focuses on the core role of VSMCs in the progression of AS, and systematically reviews the natural compounds targeting VSMCs metabolism and their molecular regulatory mechanisms. By combing the relevant pharmacological activities and potential targets, the pathological function of VSMCs in AS is further elucidated, thereby providing an important theoretical basis for the development of novel and efficient AS treatment strategies.
Shenyanshu Tablets (SYST) is a traditional Chinese patent medicine composed of 10 kinds of Chinese herbal medicines, which has the functions of tonifying the kidney and strengthening the spleen, promoting diuresis and reducing swelling. It is well known that SYST can be used to treat chronic nephritis. However, due to the complexity of the formula, the pharmacological active components in SYST that can be absorbed into plasma have not been fully studied. In this study, an ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was first developed for separating and identifying the absorbed components and metabolites of SYST in rat plasma. A total of 33 compounds were identified or preliminarily characterized, including 18 prototype components and 15 metabolites. The results demonstrated that alkaloids, fatty acids, organic acids, and triterpenoid glycosides were the main prototype components, and triterpenoid glycoside-related metabolites, fatty acid-related metabolites, and flavonoid-related metabolites were the major metabolites. These findings clarify the material basis of SYST in the treatment of chronic nephritis and provide references for further research and development of SYST.
Glycosyltransferases (GTs) are key enzymes in the glycosylation of plant secondary metabolites, primarily catalyzing the transfer of a sugar moiety from an activated donor to a specific acceptor molecule. Triterpenoid saponins, an abundant and diverse group of natural products, are composed of triterpenoid aglycones and one or more sugar chains, under the catalysis of GTs. Phytolacca Radix is a traditional Chinese medicine containing over 40 triterpenoid saponins with pharmacological values. However, the identification of glycosyltransferases related to triterpenoid saponin synthesis from Phytolacca species remains scarce. In this study, a novel glycosyltransferase, PamUGT, was identified from Phytolacca americana. PamUGT exhibits catalytic activity toward 28-/30-COOH of pentacyclic triterpenoids, and it exhibits a preference for the C-30 position when both carboxyl groups are available. To our knowledge, PamUGT is the first glycosyltransferase identified in Phytolacca species that can catalyze triterpenoids. Further analysis of substrate specificity revealed that PamUGT catalyzes the glycosylation of a wide range of compounds, including triterpenoids, flavonoids, diterpenoids, alkaloids, and phenolic acids. Our findings identify a highly promiscuous glycosyltransferase, offering a valuable enzymatic tool for modifying diverse natural products.
A high-performance thin-layer chromatography-bioautography (HPTLC-bioautography) method was developed for the rapid screening of β-lactamase inhibitors based on nitrocefin chromogenic hydrolysis. By integrating chromatographic separation with on-plate enzymatic detection, the proposed approach enables direct localization of β-lactamase inhibitory constituents from complex matrices while effectively minimizing matrix and sample color interference. Key experimental parameters were systematically optimized, and the method exhibited good flexibility by allowing screening against four different classes of β-lactamases through enzyme selection. Quantitative analysis was achieved by densitometric scanning at 525 nm, corresponding to the maximum absorption of the hydrolysis product. The method showed a limit of detection of 2 ng and a limit of quantification of 8 ng for the reference inhibitor tazobactam, along with satisfactory precision, repeatability, accuracy, and stability. The applicability of the method was demonstrated by screening extracts from twelve herbal medicines, leading to the identification of β-lactamase inhibitory zones in Perilla folium, Lonicera japonica Flos, and Lonicera Flos. Two active constituents were further characterized as rosmarinic acid and isochlorogenic acid A using online HPTLC-mass spectrometry, and their activities were verified by molecular docking and microplate-based enzymatic assay. Overall, the proposed HPTLC-bioautography strategy provides an efficient and selective analytical platform for the screening and characterization of β-lactamase inhibitors in complex natural products.
Simultaneous quantitative analysis of multiple biogenic amines (BAs) in food is challenging due to the high cost of reference standards, weak ultraviolet absorption, and complex matrix interference. To address these limitations, this study developed a strategy integrating dansyl chloride (DNS-Cl) derivatization with the quantitative analysis of multi-components by single marker (QAMS) approach to enable simultaneous quantification of nine BAs in fermented wine using HPLC-UV. A key methodological innovation of this work is the first-time adoption of a weighted scoring system for the systematic selection of the optimal internal standard (IS) for QAMS. This system comprehensively evaluates the stability of the relative correction factor (RCF), retention time suitability, and response intensity, moving beyond traditional empirical choices. Through this rigorous evaluation, tyramine (Tyr) was selected as the optimal internal standard. The established RCFs proved reproducible and stable across different instruments and operational conditions (RSD < 10%). Method validation demonstrated good linearity (R2 > 0.9985), precision (RSD < 2.28%), and accuracy (recovery: 93.92%-107.43%). Bland-Altman analysis showed that 100% of data points lay within the 95% confidence interval, demonstrating strong agreement with conventional external standard methods. In conclusion, the developed derivatization-based QAMS method is accurate, reliable, and cost-effective for the simultaneous quantification of nine biogenic amines in fermented wine, offering a practical alternative to traditional approaches. This method provides a low-cost analytical tool for quality control of BAs in fermented foods and expands the applicability of QAMS to compounds with weak UV absorption.
As a globally known medicinal and aromatic herb, Artemisia argyi (A. argyi) has excellent health benefit and economic value, especially in the field of anti-pathogenic microorganisms. At present, pathogens such as parasites, fungi, bacteria, and viruses, pose a serious threat to human health and environmentally friendly, becoming a substantial global medical burden. Researchers worldwide are focusing on developing natural antibacterial drugs. Thereinto, we collected data on the pharmacological effects of A. argyi on pathogenic microorganisms from ancient Chinese herbal texts and medical books, and the publications referring to the effects of A. argyi on bacteria, fungi, viruses, and other pathogenic microorganisms from 2005 to 2025. Simultaneously, patent searches were conducted to explore the development and utilization of the anti-pathogenic activity of A. argyi in various fields over the past 20 years. We found that A. argyi has excellent efficacy and extensive practical applications against pathogenic microorganisms. Modern studies have confirmed its inhibitory effects on common bacteria such as Escherichia coli and Staphylococcus aureus; human and crop pathogenic fungi such as Candida albicans and Aspergillus niger; and viruses such as herpes zoster virus, respiratory syncytial virus, and hepatitis B virus. Moreover, the development and application of anti-pathogenic activity of A. argyi are broad. In brief, this study provides perspectives for fully utilizing the advantages of A. argyi in anti-pathogenic effect, and supporting its potential for functional product development and applications in the fields of daily health products, agriculture and the pharmaceutical industry.
Calycosin, a pivotal isoflavonoid active constituent derived from Astragalus membranaceus, is designated as a key marker compound for the quality assessment of Astragalus and its products in the Pharmacopoeia of the People's Republic of China (2020 Edition). It exhibits a broad spectrum of pharmacological activities and holds significant potential for clinical application. This article systematically reviews the research progress on calycosin. In terms of extraction, isolation, and purification, techniques such as flash extraction and hydrolytic extraction enable efficient enrichment of the compound, whereas methods such as macroporous adsorption resin and high-speed counter-current chromatography allow for high-purity preparation. The biosynthetic pathways of calycosin encompass the phenylpropanoid pathway in planta, the chemical "one-pot" method in vitro, and synthesis via microbial cell factories, offering diverse strategies for large-scale production. Structural derivatization, particularly through modification of the 7- and 3'-hydroxyl groups, significantly enhances its solubility and antitumor activity. With respect to pharmacological mechanisms, calycosin exerts multi-pathway and low-toxicity effects in diseases such as inflammation, cancer, and neural injury by modulating multiple signaling pathways, including NF-κB, PI3K/AKT, and MAPK. Furthermore, pharmacokinetic studies indicate that its absorption depends on deglycosylation, that it undergoes substantial hepatic first-pass metabolism, and that its tissue distribution is organ-specific. Safety evaluations suggest low toxicity at therapeutic concentrations. This review aims to clarify the core issues concerning the translation of basic research on calycosin into clinical practice, thereby providing a theoretical foundation for subsequent development.
Gelsemium elegans (G. elegans) is a toxic medicinal plant traditionally used to treat chronic pain, with its toxicity linked to indole alkaloids such as gelsemine and humantenmine (HMT). Chronic pain often co-occurs with depression, a condition known to disrupt host-microbiota interactions, potentially affecting drug metabolism and toxicity. However, the impact of comorbid depression on the toxicity of G. elegans remains unclear. This study investigates how depression exacerbates the neurotoxicity of G. elegans and explores the role of the gut microbiota-host metabolic axis in this process. Depression-model mice were treated with G. elegans aqueous extract, gelsemine and HMT. Multi-omics approaches, including 16S rRNA sequencing and shotgun metagenomics, were used to analyze microbiota changes under depressive conditions. Functional validation was performed using pseudo-germ-free mice, fecal microbiota transplantation, and supplementation with Clostridium species and lithocholic acid (LCA), as well as pregnane X receptor (Pxr) knockout models. The results showed that depression significantly heightened the neurotoxicity of G. elegans, gelsemine and HMT. Mechanistically, depression reduced Clostridium abundance and LCA levels, impairing PXR activation and downregulating hepatic CYP3A11 expression. This disruption of the Clostridium-LCA-PXR-CYP3A11 axis hindered the detoxification of indole alkaloids, leading to increased systemic exposure and exacerbated neurotoxicity. Restoration of this pathway through Clostridium or LCA supplementation alleviated the toxicity. These findings highlight the role of the Clostridium-LCA-PXR-CYP3A11 axis in the altered toxicity of G. elegans in a depressive state, and suggest that Clostridium species and their metabolites may serve as a potential strategy for mitigating toxicity.
With the intensified exploration of marine resources, marine bioactive peptides have become one of the research focuses in biomedicine, food science, and materials science because of their structural diversity, unique biological activities, and broad application potential. At present, the extraction of marine peptides has expanded beyond conventional chemical extraction and enzymatic hydrolysis, with microbial fermentation and gastrointestinal simulation technologies further broadening peptide diversity. In addition, the integration of multiple chromatographic techniques with advanced detectors has significantly improved the efficiency of marine peptide identification. Owing to their diverse biological activities, including immunoregulatory, antioxidant, antibacterial, antitumor, hypotensive, and hypoglycemic effects, marine peptides not only enrich the pool of candidates for marine drug development but also provide new perspectives for addressing numerous health challenges. Importantly, substantial progress has been made in the screening, identification, and mechanistic elucidation of marine bioactive peptides, driven by advances in high-throughput technologies and the bioinformatics. However, marine peptide research still faces several challenges, including complex sourcing, difficulties in large-scale acquisition, and insufficient exploration of biological activities. Therefore, this article concisely reviews recent progress in the extraction, purification, and identification of marine bioactive peptides, summarizes current research on their biological activities, and highlights the application of bioinformatics in marine peptide studies.
Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to the absence of effective targeted therapies. In this study, we demonstrate that elevated expression of microtubule affinity-regulating kinase 2 (MARK2), but not other MARK family members (MARK1, MARK3, and MARK4), correlates with poor prognosis in TNBC patients. Silencing MARK2 impairs TNBC progression via inhibition of mutant p53 (mutp53) signaling. In contrast, silencing any of the other three MARKs either enhances or does not affect TNBC cell growth or migration and has no impact on mutp53 expression. Notably, direct knockdown of mutp53 recapitulates the effects of MARK2 ablation in TNBC cells, further supporting a functional linkage. Moreover, ectopic expression of either wild-type (WT) MARK2 or its kinase-dead (KD) mutant enhances mutp53 signaling and promotes TNBC progression; however, MARK2 overexpression does not alter wild-type p53 (wtp53) expression or cell growth in luminal breast cancer cells. Significant inverse correlations are also observed between the expression levels of MARK2, THBS1, or HBEGF (two direct target genes of mutp53) and both overall and disease-free survival in TNBC patients harboring mutTP53, whereas no such association exists between MARK2 and survival in breast cancer subtypes expressing wtTP53. MARK2 is predominantly localized in the nucleus of TNBC cells, where it interacts with and stabilizes mutp53 through its UBA and Spacer domains. Consistent with this, MARK2-ΔUBA or MARK2-ΔSpacer mutant proteins fail to bind mutp53 or sustain its signaling, thereby acting as dominant-negative inhibitors that suppress TNBC progression. Collectively, our findings indicate that suppressing MARK2 expression, rather than inhibiting its kinase activity, may represent an effective therapeutic strategy for TNBC with mutTP53.
Type 2 diabetes mellitus (T2DM) is fundamentally linked to gut microbiota dysbiosis, a condition that triggers a cascade of pathophysiological changes including aberrant host-microbe co-metabolism, compromised intestinal barrier integrity, and chronic low-grade inflammation, which collectively drive insulin resistance. While conventional therapies have limitations, traditional Chinese medicine (TCM) presents a promising therapeutic strategy. This review comprehensively elucidates the pathophysiological link between gut dysbiosis and T2DM. It then systematically summarizes the multi-target mechanisms by which TCM exerts its therapeutic effects, including: remodeling the gut microbial ecosystem; reprogramming host-microbe co-metabolism of short-chain fatty acids (SCFAs), bile acids (BAs), and branched-chain amino acids (BCAAs); reinforcing the intestinal barrier to mitigate metabolic endotoxemia; and modulating key signaling pathways involved in inflammation and immunity, etc. Key clinical evidence is also summarized. Furthermore, the review critically evaluates the preclinical and clinical evidence supporting these mechanisms, highlighting both therapeutic potential and current challenges, such as the need for standardization. Finally, current limitations and future prospects are considered, proposing a path forward for integrating microbiota-targeted TCM therapies into the modern, evidence-based management of T2DM.
Cholesterol metabolism disorders are a major contributor to type 2 diabetes mellitus (T2DM). Cholesterol accumulation in the liver exacerbates insulin resistance, while cholesterol overload in the pancreatic islets impairs insulin secretion. Peroxisome proliferator activated receptors (PPARs) are considered potential therapeutic targets for cholesterol regulation. Herein, we report a series of novel aromatic amide derivatives as pan-PPAR agonists. Among them, compound 15a exhibited potent and well balanced pan-PPAR agonistic activity and significantly upregulated the expression of ATP binding cassette transporter A1 (ABCA1), a PPAR target gene involved in cholesterol efflux. In a high fat and high sucrose diet induced KKAy diabetic mouse model, 15a markedly reduced plasma cholesterol levels, hepatic cholesterol accumulation, and islet cholesterol deposition. It also demonstrated favorable regulation of glucolipid metabolism, leading to pronounced alleviation of hepatic steatosis and islet dysfunction, while avoiding the weight gain and adiposity side effects associated with PPARγ agonists. SPR experiments demonstrated that 15a interacts with the ligand binding domains (LBDs) of all three PPAR subtypes. Molecular docking and single point mutation assays of key residues confirmed that 15a likely exerts its pan PPAR agonist activity by stabilizing helix 3 of the three PPAR subtypes. Furthermore, 15a exhibits improved pharmacokinetic properties and a favorable safety profile compared to the lead compound. In summary, this study demonstrates that compound 15a significantly ameliorates hepatic steatosis and islet dysfunction associated with T2DM by regulating cholesterol metabolism disorders along the liver-islet axis, highlighting its strong potential for treating hepatic lipid accumulation and T2DM related islet dysfunction.
Costunolide, a natural germacranolide sesquiterpenoid, exhibits only moderate anti-HCC activity. To enhance its efficacy and tumor selectivity, a series of 37 dimeric costunolide-1,2,3-triazole conjugates was designed and synthesized by integrating dimerization and molecular hybridization strategies. Evaluation of their antiproliferative effects on HepG2, Huh-7, and SK-Hep-1 cells suggested that 25 compounds were more potent than either costunolide or sorafenib. The most active dimer 19 exhibited significant activity with IC50 values of 1.6, 1.3, and 0.7 μmol·L-1, which were 13.1, 14.2, and 34.9-fold greater than those of costunolide. Compound 19 showed favorable selectivity against human normal liver cells (THLE-2) and markedly inhibited colony formation. Through a combination of bioinformatics, docking, and molecular dynamics (MD) simulations, glucose-6-phosphate dehydrogenase (G6PD) was identified as a target of compound 19, which was subsequently validated by DARTS and SPR assays. Functional studies revealed that compound 19 arrested the HCC cell cycle at the G2/M phase, suppressed migration and invasion by inhibiting epithelial-mesenchymal transition, and triggered both apoptosis and ferroptosis. These findings establish triazole-linked costunolide dimer 19 as a promising lead candidate for the development of novel anti-HCC therapies.
Oncolytic peptides have emerged as a distinct class of antitumor agents with the potential to overcome therapeutic resistance and enhance anticancer immunity. Most oncolytic peptides are naturally derived or structurally inspired by natural peptides, and typically display cationic and amphipathic features. Mechanistically, these physicochemical properties enable preferential binding to the negatively charged membranes of cancer cells and subsequent membrane disruption. Beyond direct membrane lysis, many naturally derived oncolytic peptides (NDOPs) perturb intracellular organelle membranes, trigger immunogenic cell death, and modulate immune cells and immune checkpoints, thereby amplifying the cancer-immunity cycle. Through these multifaceted mechanisms, NDOPs show a low tendency to induce drug resistance and can enhance response rates when combined with conventional therapies. Notably, four NDOP-based agents have advanced into clinical trials, underscoring their translational promise. In this review, we summarize the sources, structural features, and mechanisms of NDOPs, highlight innovative therapeutic applications and rational combination strategies, and further discuss the current clinical progress. We also outline key challenges and future directions for the development of NDOPs as next-generation anticancer therapeutics.
As a medicinal and edible herb, the quality grade of Codonopsis Radix (CR) is the key determinant of its market price. However, the current grading system remains significantly inadequate. Single-dimensional indices (including phenotypic traits, chemical components, or bioactivity) fail to accurately characterize the comprehensive quality of CR. Under this circumstance, this study established a multidimensional quality evaluation system integrating phenotypic traits, chemical components, and bioactivity. A multi-index weighted quality comprehensive evaluation index (QCEI) was constructed by combining the entropy weight method (EWM), criteria importance through inter-criteria correlation (CRITIC) method, technique for order preference by similarity to ideal solution (TOPSIS) method, and triangular area method. Hierarchical cluster analysis (HCA) based on QCEI classified 50 CR batches into 3 grades: Grade I (QCEI≥0.56, excellent quality), Grade II (0.38 ≤ QCEI<0.56, good quality), and Grade III (QCEI<0.38, general quality). In vivo validation showed a significant positive correlation between QCEI grades and immunomodulatory effects. Specifically, the CR of Grade I significantly enhanced the body weight growth rate, elevated thymus and spleen indices, and regulated serum levels of IL-2, IL-6, and TNF-α in immunosuppressed mice (p < 0.05-p < 0.0001). This study establishes a scientific and reliable quality grading standard for CR, providing a valuable reference for the comprehensive quality evaluation of other traditional Chinese medicinal materials.
Self-assembled nanoaggregates (SANs) derived from herbal decoctions have emerged as promising natural nanomedicines. However, their formation patterns in multi-herb formulations and therapeutic roles in central nervous system disorders remain unclear. Wuzhuyu decoction (WZYD) is a classical formula for migraine treatment. Here, we reveal that SANs in WZYD (N-WZYDs) are formed through synergistic interactions among multiple herbal ingredients with Euodiae Fructus as the focus. N-WZYDs consisted mainly of proteoglycan scaffolds and small-molecule active components. In chronic migraine (CM) rat models, N-WZYDs significantly alleviated symptoms with efficacy comparable to that of WZYD, potentially via inhibition of the IL-33/ST2/TRPA1 signaling pathway. In Caco-2 cells, transport studies indicated that ginsenoside Rg1, dehydroevodiamine, and rutaevin were poorly absorbed, whereas evodiamine and 6-gingerol were moderately absorbed but significantly active in efflux, indicating the intestine as a key site of action. As an oral medication, intact N-WZYDs accumulated primarily in the intestines and could be internalized by Caco-2 and enterochromaffin cells. Crucially, N-WZYDs promoted serotonin release from enterochromaffin cells more effectively than free active molecules alone and increased peripheral serotonin levels, thereby alleviating CM. By investigating the formation patterns, anti-CM mechanisms, and absorption behaviors of N-WZYDs, this study elucidated their material basis and brain-intestine interactions in treating CM, supporting their further development as therapeutic agents or drug delivery systems.
Early diagnosis of colorectal cancer (CRC) can significantly improve prognosis, but currently there is a lack of simple and effective screening methods in clinical practice. This single-center retrospective study included patients with CRC and benign colorectal polyps (BCP) diagnosed at our hospital between December 2020 and December 2023, as well as healthy controls (HCs). Eligible participants were randomly assigned to a training cohort and an internal validation cohort in a 7:3 ratio. Univariable and multivariable logistic regression analyses were performed in the training cohort to identify independent diagnostic predictors of CRC. A diagnostic nomogram was then constructed based on these predictors and internally validated. Six hundred forty seven CRC, 365 BCP, and 400 HC were ultimately included in the study. Univariate and multivariate analysis showed that sex, HB, CEA, CA19-9, CONUT score, and HALP score were independent diagnostic predictors associated with CRC. The internal validation results indicated that the predictive ability of the nomogram (AUCnomogram = 0.896) is significantly stronger than that of each individual indicator (AUCHB = 0.78, AUCCEA = 0.73, AUCCA19-9 = 0.72, AUCCONUT = 0.64, AUCHALP = 0.72) (p < 0.05). The calibration curves confirmed the high consistency between the predicted probability and observed probability of the nomogram, and the decision curve analysis demonstrated its good clinical utility. This study integrated multiple independent diagnostic predictors of CRC and developed an internally validated diagnostic nomogram with good discrimination and calibration in this single-center retrospective cohort.